A principal goal of this project is to elucidate pathogenic mechanisms in immunologically mediated tubular and interstitial renal disease in experimental animals and man. The model of antitubular basement membrane (anti TBM) disease in guinea pigs in being studied in particular with respect to the role of IgG and IgG antibodies in the mediation of the renal damage, the nature and function of the infiltrating mononuclear cells, and the factors involved in the initiation of autoantibody response against the TBM. The idiotypic restriction of the autoantibodies is under investigation. Other studies are concerned with the participation of cell mediated mechanisms in the production of glomerular damage in an experimental model of glomerulonephritis, the factors influencing the intraglomerular localization of immune complexes in rats with Heymann nephritis, the antigenic determinants reactive with anti GBM antibodies in patients with Goodpasture's syndrome, the role of cold insoluble globulin in renal disease and the relationship between levels of circulating immune complexes, as detected by the Raji cell assay, in the various forms of glomerular disease.